Parallel processing is a common principle across different sensory systems. The brain tends to encode different aspects of a sensory stimulus into separate projection pathways for carrying out unique processing optimized for dedicated features. Though parallel pathways are well studied in other sensory modalities, it remains unclear how olfactory signals are transmitted to high-order centers through similar parallel-processing circuits. In this grant, I propose to explore this issue by focusing on the two major types of projection neurons in the olfactory bulb, the mitral and tufted cells. While early analyses of neuronal morphology suggest that they may represent two separate pathways for odor processing, their functional distinctions have not yet been well characterized. This is mainly due to the fact that it is difficult to compare the odor-response properties without knowing whether interested neurons receive olfactory inputs from common or different glomeruli. Furthermore, it is not clear whether these cells have different axonal projections into the olfactory tubercle and piriform cortex. To address these two questions, I will take advantage of my recently developed approach, which combines dextran-dye local electroporation and in vivo two-photon calcium imaging to achieve simultaneous tracing of neural circuits and imaging of cellular functions. A systematic comparative analysis will be carried out on the odor response profiles of mitral and tufted cells sharing a common glomerular input, in search for insights into how they are differently involved in coding and processing different odor features. Based on my current preliminary data, I will further test the hypothesis that mitral and tufted cells display different preferences of their axonal termination fields. With these two series of experiments, I expect to ultimately establish, from both the functional and circuitry points of view, that mitral and tufted cells indeed constitute two parallel processing pathways handling different sets of odor information. Public Health Relevance: All sensory systems essentially provide a parallel interface between our brain and external environment. Neural mechanisms underlying the parallel processing of sensory inputs have already been well studied in the visual and auditory systems. However, for the sense of smell, which contributes critically to our daily life quality, it remains so far poorly understood how such parallel signal-processing mechanisms are implemented in this system, especially at the neuronal-circuit level. I here propose a series of experiments to test the hypothesis that the two major types of principal neurons in the olfactory bulb, the mitral and tufted cells, display quite different odor response profiles and central axonal projection patterns. Such differences enable these neurons to function as the backbone in two parallel odor-processing pathways, which are involved in processing different aspects of odor information.